PB2455: THE DARK SIDE OF FECAL MICROBIOTA TRANSPLANTATION IN REFRACTORY ACUTE GASTROINTESTINAL GRAFT VERSUS HOST DISEASE.
Authors: Oumayma Hari, Rayane Berrahouane, Agathe Artiaga, Lilia Simonetti, Benoit Tisserand, Charles Herbaux, Guillaume Cartron, Patrice Ceballos
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Gastrointestinal tract graft-versus-host disease (GI-GvHD) is a major cause of morbidity and mortality after allogenic hematopoietic stem cell transplantation (allo-HCT). The initial therapy by corticosteroids has an unsatisfactory effectiveness with only 50% of response. Patients with steroid-refractory GI-GvHD (SR GI-GvHD) have a poor prognosis with no standardized therapeutic options. Recent studies of intestinal flora suggested its role in GI-GvHD, then the use of fecal microbiota transplantation (FMT) appears safe and becomes an attractive option in salvage therapy of SR GI-GvHD. Aims: Our work mainly aimed to identify safety and efficacity of Fecal Microbiota Transplantation in SR GI-GvHD and to identify risk factors of non tolerance. Methods: Our study included all FMT realized for patients with SR GI-GvHD. Steroid-resistanc was defined as GI-GvHD that did not improve within 7 days after initial steroid therapy (1 mg/kg of methylprednisolone) or progressed after 5 days of treatment. Before stool collection, a questionnaire was used to screen donors about risk factors of potentially transmissible diseases, history of bowel or metabolic diseases, and antibiotic use. Subsequent screening of stool samples and blood culture were perform to exclude donors carrying infectious pathogens agents. FMT were derived from 6 to 8 healthy donors and were administered as frozen liquid fecal material via endoscopy (coloscopy). Results: Between December 2021 and September 2022, we realized nine FMT in three different patients presenting SR GI-GvHD, they were allo-HCT for chronic myeloid leukemia, multiple myeloma and acute myeloblastic leukemia. Before and during FMT, patients were receiving a median methylprednisolone dose of 1.7 mg/kg and additional GvHD treatments including cyclosporin, methotrexate and ruxolitinib. On the day of FMT, side effects reported by patients included cramp and abdominal discomfort, no other complications were seen, these symptoms resolved spontaneously within hours. During a median follow up of 38 months, infectious complications were predominant, all patients developed at least one infection during the first month following FMT. These included two cases of sepsis secondary to bacteremia caused by Veillonella Parvula and Escherichia Coli (3 and 10 days after FMT respectively); one case of endocarditis due to Staphylococcus aureus meticilino-sensible (5 days after FMT) in a patient with aortic prosthesis, a reactivation of Cytomegalovirus detected in a seropositive patient (day 30 of FMT) and one case of pneumonia (7 days after FMT) (Figure 1). To preserve the new intestinal flora, large spectrum antibiotics were only used when vital prognosis was engaged. Otherwise, none of the patients developed fungal infection during the follow up. As late gastro-intestinal complications, we noted the occurrence of a fatal occlusive syndrome and hematochezia in two patients on day 38 and 45 respectively. Cardio-vascular complications were also present, including pulmonary embolism causing death in the patient with aortic prothesis.Figure1: Scannographic image of a right superior lobal anterior sub pleural condensation Concerning response, all patients had partial response a week after FMT. Actually, the patient alive has normal stool frequency and consistency with reduction of abdominal cramps, corticosteroids and immunosuppressive medication were discontinued after a progressive tapering and close supervision. Summary/Conclusion: Fecal microbiota transplantation is becoming a growing therapy in SR GI-GvHD, the evolution of patients appears favorable and largely free of severe adverse events. However, recipients should be well aware of its potential risks. Keywords: Allogeneic stem cell transplant, Graft-versus-host disease (GVHD)